Pegcetacoplan for Adolescents with C3 Glomerulopathy or Primary Immune Complex Membranoproliferative Glomerulonephritis: Phase 3 VALIANT Subgroup Analysis

Abstract

Background – In VALIANT (phase 3; NCT05067127), pegcetacoplan (C3/C3b inhibitor) led to significant proteinuria reduction (>68% vs placebo) and estimated glomerular filtration rate (eGFR) stabilization in native kidney and posttransplant recurrent C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). Here, we describe results for adolescents (12–17 years) in VALIANT. Methods – Patients (randomized 1:1) received pegcetacoplan twice weekly or placebo for 26 weeks. For overall population, the primary endpoint was baseline-to-week 26 change in log-transformed urine protein-to-creatinine ratio (UPCR) in pegcetacoplan vs placebo arms. Key secondary endpoints were: patients achieving composite renal endpoint (≤15% eGFR reduction and ≥50% UPCR reduction), patients achieving ≥50% UPCR reduction, and eGFR change. Results – Twenty-eight adolescents received pegcetacoplan; 27 received placebo. Consistent with overall population, pegcetacoplan-treated adolescents achieved clinically meaningful UPCR reduction (relative reduction, 75% [95% confidence interval (CI)], 59 to 84; nominal P < 0.001). More adolescents in pegcetacoplan vs placebo arms achieved the composite endpoint (57% vs 4%; nominal P = 0.002) and ≥50% UPCR reduction (71% vs 4%; nominal P < 0.001). eGFR was stable for pegcetacoplan-treated adolescents (adjusted least squares mean difference [95%] vs placebo, +9.7 [-0.026 to 19.382] mL/min/1.73 m2; nominal P = 0.05). Three adolescents in each group experienced serious treatment-emergent adverse events (pyrexia in 1 pegcetacoplan-treated patient was considered treatment related). None experienced infection caused by encapsulated bacteria. Conclusions – Pegcetacoplan induced clinically meaningful proteinuria reduction and eGFR stabilization compared with placebo in adolescents with C3G or primary IC-MPGN and was well tolerated.